【精华】Anesthesiology，A&A 摘要翻译

GoalYou

【第365篇】多巴胺D1受体活化促进异氟烷全身麻醉苏醒 Anesthesiology.2013 Jan;118(1):30-39.

Activation of D1 Dopamine Receptors Induces Emergence from Isoflurane General Anesthesia.

Taylor NE, Chemali JJ, Brown EN, Solt K.

* Clinical Fellow, Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, and Resident, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. ? Research Assistant, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital. ? Anesthetist, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital; Warren M. Zapol Professor, Department of Anaesthesia, Harvard Medical School; Professor of Computational Neuroscience, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts; Professor of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology. § Assistant Professor, Department of Anaesthesia, Harvard Medical School; Assistant Anesthetist, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital; and Research Affiliate, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology.

Abstract

BACKGROUND: A recent study showed that methylphenidate induces emergence from isoflurane anesthesia. Methylphenidate inhibits dopamine and norepinephrine reuptake transporters. The objective of this study was to test the hypothesis that selective dopamine receptor activation induces emergence from isoflurane anesthesia.
METHODS: In adult rats, we tested the effects of chloro-APB (D1 agonist) and quinpirole (D2 agonist) on time to emergence from isoflurane general anesthesia. We then performed a dose-response study to test for chloro-APB-induced restoration of righting during continuous isoflurane anesthesia. SCH-23390 (D1 antagonist) was used to confirm that the effects induced by chloro-APB are specifically mediated by D1 receptors. In a separate group of animals, spectral analysis was performed on surface electroencephalogram recordings to assess neurophysiologic changes induced by chloro-APB and quinpirole during isoflurane general anesthesia.
RESULTS: Chloro-APB decreased median time to emergence from 330 to 50 s. The median difference in time to emergence between the saline control group (n = 6) and the chloro-APB group (n = 6) was 222 s (95% CI: 77-534 s, Mann-Whitney test). This difference was statistically significant (P = 0.0082). During continuous isoflurane anesthesia, chloro-APB dose-dependently restored righting (n = 6) and decreased electroencephalogram δ power (n = 4). These effects were inhibited by pretreatment with SCH-23390. Quinpirole did not restore righting (n = 6) and had no significant effect on the electroencephalogram (n = 4) during continuous isoflurane anesthesia.
CONCLUSIONS: Activation of D1 receptors by chloro-APB decreases time to emergence from isoflurane anesthesia and produces behavioral and neurophysiologic evidence of arousal during continuous isoflurane anesthesia. These findings suggest that selective activation of a D1 receptor-mediated arousal mechanism is sufficient to induce emergence from isoflurane general anesthesia.

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多巴胺D1受体活化促进异氟烷全身麻醉苏醒

背景：最近的一项研究表明哌醋甲酯促进异氟烷全身麻醉苏醒。哌醋甲酯能够抑制多巴胺和去甲肾上腺素的再摄取。本研究旨在验证选择性活化多巴胺受体可促进异氟烷全身麻醉苏醒的假说。

方法：在成年大鼠中，我们检测多巴胺D1受体激动剂（chloro-APB）和D2受体激动剂（quinpirole）对异氟烷全身麻醉苏醒时间的影响。然后，我们对chloro-APB促进持续异氟烷全身麻醉大鼠翻正反射恢复的作用进行剂量相关性研究。D1受体抑制剂（SCH-23390）用于证实chloro-APB通过选择性作用于D1受体发挥促进苏醒的作用。在单独一组动物中，我们对记录到的脑电图进行频谱分析，进而评价在持续异氟烷全身麻醉时chloro-APB和quinpirole对神经生理学影响。

结果：chloro-APB将苏醒中位时间从330s降低到50s。生理盐水组（n=6）和chloro-APB组（n=6）苏醒时间差值的中位数为222s（95% 可信区间: 77-534 s, Mann-Whitney test）。差异具有统计学意义（p=0.0082）。在异氟烷持续麻醉时，chloro-APB剂量依赖性促进翻正反射恢复（n=6）和减少δ 脑电波的活动（n=4）。通过SCH-23390预处理可抑制该作用。在异氟烷持续麻醉时，Quinpirole组未出现翻正反射恢复（n=6）及对脑电图无明显影响（n=4）。

结论：D1受体活化减少异氟烷全身麻醉的苏醒时间，觉醒行为学和神经生理学的证据明其在异氟烷持续全身麻醉时能够促进觉醒。这些发现提示，选择性激活D1受体足以导致异氟烷全身麻醉的苏醒。

GoalYou

【第364篇】硬膜外药物及手术对开放性肾脏手术后膀胱功能的影响：一项临床随机试验研究 Anesthesiology.2013 Jan;118(1):70-7.

Influence of epidural mixture and surgery on bladder function after open renal surgery: a randomized clinical trial.

Wuethrich PY, Metzger T, Mordasini L, Kessler TM, Curatolo M, Burkhard FC.

* Consultant in Anesthesia, § Professor, Department of Anesthesiology and Pain Therapy, ? Resident, ‖ Professor and Vice Chair-woman, Department of Urology, University Hospital Bern, Berne, Switzerland. ? Head of Neuro-Urology, Spinal Cord Injury Center and Research, University of Zürich, Balgrist University Hospital, Zürich, Switzerland.

Abstract

BACKGROUND: In a previous observational study, thoracic epidural analgesia (TEA) after open renal surgery resulted in clinically relevant postvoid residuals (PVRs). This study aimed to investigate the individual contribution of epidurally administrated drugs and surgery in bladder dysfunction.

METHODS: In this single-center, parallel-group, randomized (computer-generated list), double-blind superiority trial, 40 patients undergoing open renal surgery were equally allocated to receive epidural bupivacaine (0.125%) alone or with fentanyl (2 ?g/ml). Patients underwent urodynamic investigations before TEA and during TEA preoperatively and postoperatively. Primary outcome was the difference (Δ) in PVR between before TEA and postoperatively during TEA. Secondary outcomes were changes in detrusor pressure at maximum flow rate, bladder compliance, and ΔPVR between different time points.

RESULTS: Median ΔPVR (ml) from baseline to postoperatively was 180 (range, -85 to 645; P = 0.001) in the bupivacaine group and 235 (range, 0-580; P value less than 0.001) in the bupivacaine/fentanyl group, with no difference between groups (95% confidence interval, -167 to 103; P = 0.634). Detrusor pressure at maximum flow rate (cm H2O) from baseline was more pronounced in the bupivacaine/fentanyl than that in the bupivacaine group preoperatively (-10; range, -64 to -2; P value less than 0.001 vs. -3; range, -35 to 13; P = 0.397) (P = 0.045) and postoperatively (-18; range, -64 to 0; P value less than 0.001 vs. -12; range, -34 to 22; P = 0.006) (P = 0.135). Surgery did not affect PVRs, but a decreased bladder compliance was observed in both groups. No adverse events occurred.

CONCLUSIONS: Thoracic epidurally administrated bupivacaine resulted in clinically relevant PVRs based on impaired detrusor function. The addition of fentanyl enhanced this effect without generating greater PVRs. After surgery, the voiding phase was not further impaired; however, bladder compliance was decreased.

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硬膜外药物及手术对开放性肾脏手术后膀胱功能的影响：一项临床随机试验研究

【摘要】

背景：在之前的一项观察性研究发现，开放性肾脏手术术后采用胸段硬膜外镇痛（TEA）可导致临床相关的尿液残留（PVRs）。该研究旨在研究硬膜外注射药物和手术各自对膀胱功能的影响。

方法：该研究为单中心随机对照双盲试验，40位接受开放性肾脏外科手术的病人随机分为两组。一组接受硬膜外布比卡因（0.125%）注射，另一组接受硬膜外布比卡因和芬太尼（2 ?g/ml）注射。在TEA之前、术前TEA过程中、及术后检测尿动力学变化。研究的主要结果为TEA前和术后TEA中PVR的差别。次要结果包括最高流量时逼尿肌的压力、膀胱顺应性和不同时间点PVR的差别。

结果：布比卡因组，PVR基线值（注：查看全文后“基线值”为TEA前检测值）与术后PVR差值的中位数为180（范围，-85 ~ 645；P = 0.001），布比卡因/芬太尼组为235（范围，0-580；P < 0.001），两组差异无统计学意义（95%可信区间-167~103；P = 0.634）。术前布比卡因/芬太尼组最大流速时逼尿肌的压力值（注：该处指的是“术前TEA后”检测值）与基线值的差值较布比卡因组明显(-10；范围，-64 ~ -2；P< 0.001 vs. -3；范围，-35 ~ 13；P = 0.397) (P = 0.045) ，术后亦如此 (-18；范围， -64 to 0; P value less than 0.001 vs. -12；范围， -34 ~ 22; P = 0.006) (P = 0.135)。手术对PVRs没有影响，但在两组均发现膀胱的顺应性下降。无不良反应发生。

结论：胸段硬膜外注射布比卡因通过影响逼尿肌的功能导致临床相关PVRs。联合注射芬太尼增强对逼尿肌功能的影响，但未发现导致更严重的PVRs。手术对排空期无进一步影响；然而，膀胱的顺应性下降。

GoalYou

【第363篇】吸入含氢气的混合气体可减少新生小鼠暴露于七氟烷后的神经元凋亡及继发的行为异常 Anesthesiology. 2013 Jan;118(1):105-13

Coadministration of hydrogen gas as part of the carrier gas mixture suppresses neuronal apoptosis and subsequent behavioral deficits caused by neonatal exposure to sevoflurane in mice.

Yonamine R, Satoh Y, Kodama M, Araki Y, Kazama T.

* Assistant Professor, ? Associate Professor, ? Postgraduate Student, § Professor and Chairman, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Saitama, Japan.

Abstract

BACKGROUND: In animal models, several anesthetics induce widespread increases in neuronal apoptosis in the developing brain with subsequent neurologic deficits. Although the mechanisms are largely unknown, the neurotoxicity may, at least in part, be due to elevated oxidative stress caused by mitochondrial dysfunction. In an investigation of potential therapies that could protect against this type of damage, we studied the effects of molecular hydrogen on anesthetic-induced neurotoxicity in the developing mouse brain.

METHODS: Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h with or without hydrogen (< 1.3%) as part of the carrier gas mixture. Apoptosis was evaluated by immunohistochemical staining for cleaved caspase-3 (n = 8-10/group). Western blot analysis for cleaved poly-(adenosine diphosphate-ribose) polymerase was also performed to examine apoptosis (n = 3-6/group). Oxidative stress was assessed by immunohistochemical staining for 4-hydroxy-2-nonenal (n = 8/group). Long-term memory and social behavior were examined using the fear conditioning test and the sociability test, respectively (n = 18-20/group).

RESULTS: Western blot analysis showed that coadministration of 1.3% hydrogen gas significantly (P < 0.001) reduced the level of neuronal apoptosis to approximately 40% compared with sevoflurane exposure alone. Immunohistochemical analysis showed that hydrogen reduced oxidative stress induced by neonatal sevoflurane exposure. Although neonatal sevoflurane exposure caused impairment in long-term memory and abnormal social behaviors in adulthood, mice coadministered hydrogen gas with sevoflurane did not exhibit these deficits.

CONCLUSIONS: Inhalation of hydrogen gas robustly decreased neuronal apoptosis and subsequent cognitive impairments caused by neonatal exposure to sevoflurane.

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吸入含氢气的混合气体可减少新生小鼠暴露于七氟烷后的神经元凋亡及继发的行为异常

【摘要】

背景：在动物模型中，一些麻醉药物导致大脑发育过程中神经元凋亡增加并继发功能障碍。尽管该机制十分不明确，但认为其神经毒性作用可能一部分与线粒体功能障碍导致的氧化应激损伤有关。为了探索该损伤可能的治疗方法，本实验对氢气在麻醉药物导致小鼠大脑发育过程神经毒性中的作用进行研究。

方法：出生6天的C57BL/6小鼠分别暴露于含有氢气（<1.3%）和不含氢气的七氟烷（3%）中6小时。通过免疫组化检测cleaved caspase-3作为凋亡的指标（n=8-10 每组）。Western blot方法检测多聚腺苷酸二磷酸核糖聚合酶作为凋亡指标（n=3-6 每组）。免疫组化的方法检测4-羟基壬烯醛（4-hydroxy-2-nonenal）作为氧化应激损伤的指标（n=8 每组）。长时记忆和社会活动分别通过恐惧条件化测试（fear conditioning test）和社交能力测试（sociability test）（n=18-20 每组）。

结果：Western blot检测结果发现联合吸入1.3%氢气组与只吸入七氟烷组相比神经元凋亡率下降约40%（P<0.001）。免疫组化研究表明氢气减少新生小鼠七氟烷暴露后的氧化应激反应。尽管，新生小鼠暴露于七氟烷可导致其成年后不可恢复的长时记忆功能和社交能力障碍，但联合吸入氢气组小鼠未表现出这些功能障碍。

结论：吸入氢气可明显减少新生期暴露于七氟烷而导致的神经元凋亡及认知功能障碍。

GoalYou

【第362篇】脂多糖刺激单核细胞通过NFKB1基因启动子-94ins/delATTG影响NFKB1的核转位并增加脓毒症死亡率Anesthesiology. 2013 Jan;118(1):123-133.

The NFKB1 Promoter Polymorphism (-94ins/delATTG) Alters Nuclear Translocation of NF-κB1 in Monocytes after Lipopolysaccharide Stimulation and Is Associated with Increased Mortality in Sepsis.

Adamzik M, Sch?fer S, Frey UH, Becker A, Kreuzer M, Winning S, Frede S, Steinmann J, Fandrey J, Zacharowski K, Siffert W, Peters J, Hartmann M.

* Associate Professor, ? Research Assistant, ? Medical Student, ?? Professor, Klinik für An?sthesiologie und Intensivmedizin, § Associate Professor, ‖ Professor, Institut für Physiologie, # Research Assistant, Institut für Medizinische Mikrobiologie, ?? Professor, Institut für Pharmakogenetik, Universit?t Duisburg-Essen, Universit?tsklinikum Essen, Essen, Germany. ** Professor, Klinik für An?sthesiologie, Intensivmedizin und Schmerztherapie, Klinikum der Goethe Universit?t Frankfurt, Frankfurt, Germany.

Abstract

BACKGROUND: Because the nuclear factor-κB (NF-κB) coupled pathway is believed to amplify inflammation prevailing in sepsis, the authors tested the hypotheses that the insertion-deletion polymorphism (-94ins/delATTG) (1) alters nuclear translocation of nuclear factor-κB and activator protein-1 (NF-κB1) in monocytes after lipopolysaccharide stimulation; (2) affects lipopolysaccharide-induced NF-κB1 messenger RNA expression, tumor necrosis factor α concentrations, and tissue factor activity; and (3) may be associated with increased 30-day mortality in patients with sepsis.

METHODS: Nuclear translocation of NF-κB1 in monocytes after lipopolysaccharide stimulation from healthy blood donors was performed with immunofluorescence staining (n = 5 each). Lipopolysaccharide-induced NF-κB1 messenger RNA expression was measured with real-time polymerase chain reaction (PCR; n = 60), tumor necrosis factor α concentrations with a multiplexing system kit (n = 60), and tissue factor activity with thromboelastometry (n = 105). In a prospective study, multivariate proportional hazard analysis tested 30-day mortality in patients with sepsis (n = 143).

METHODS AND RESULTS: The homozygous deletion genotype compared with the homozygous insertion genotype was associated with a nearly twofold increase in nuclear translocation of NF-κB1 (P = 0.001), a threefold difference in NF-κB1 messenger RNA expression (P = 0.001), and a twofold increase in tissue factor expression (P = 0.021). The deletion allele in adults with severe sepsis was tested as an independent prognostic factor for 30-day mortality (hazard ratio, 2.3; 95% CI, 1.13-4.8; P = 0.022). Mortality was 25% for homozygous insertion genotypes but 41% for combined heterozygous deletion/homozygous deletion genotypes (P = 0.034).

CONCLUSION: The deletion allele of the NFκB1 insertion-deletion (-94ins/delATTG) polymorphism is associated with increased 30-day mortality in patients with severe sepsis and increased reaction of the innate immune system.

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脂多糖刺激单核细胞通过NFKB1基因启动子-94ins/delATTG影响NFKB1的核转位并与增加脓毒症死亡率

【摘要】

背景： 由于NF-KB耦合途径可放大脓毒症的炎症反应，因此本研究中我们对下述假设进行验证，基因启动子-94ins/delATTG的插入/缺失突变（1）是否改变单核细胞NF-KB和活化因子-1（NF-KB1）的核转位；（2）是否影响脂多糖诱导NFKB1信使RNA的表达，肿瘤坏死因子的浓度和组织因子的活性；（3）是否与脓毒症患者30天死亡率增加有关。

方法：通过免疫荧光染色方法检测健康献血者的单核细胞被脂多糖刺激后NFKB1的核转位（n=5）。在一项前瞻性研究中，通过多元比例风险分析测试脓毒症患者30天死亡率（n=143）。

结果：纯和基因缺失型与纯和基因嵌入型相比，NFKB1核转位几乎是它的两倍（P = 0.001），NFKB1信使RNA的表达是它的3倍（P = 0.001），组织因子表达是它的2倍（P = 0.021）。严重脓毒血症成年患者该等位基因缺失是30天死亡的独立预测因素 (风险比， 2.3； 95% CI，1.13-4.8；P = 0.022)。纯和基因嵌入型的死亡率为25%，而混合杂合缺失或纯和缺失型的死亡率为41% (P = 0.034)。

结论：NF-κB1基因启动子-94ins/delATTG的缺失与严重脓毒症患者30天死亡率增加有关，增强先天免疫系统反应。

GoalYou

【第361篇】全身应用多奈哌齐通过胆碱能和γ-氨基丁酸机制减轻神经损伤后的高敏反应Anesthesiology. 2013 Jan;118(1):173-80.

Relief of Hypersensitivity after Nerve Injury from Systemic Donepezil Involves Spinal Cholinergic and γ-Aminobutyric Acid Mechanisms.

Kimura M, Hayashida K, Eisenach JC, Saito S, Obata H.

* Graduate Student, § Professor of Anesthesiology, ‖ Associate Professor of Anesthesiology, Department of Anesthesiology, Gunma University Graduate School of Medicine, Maebashi, Japan. ? Assistant Professor of Anesthesiology, ? FM James, III Professor of Anesthesiology and Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Abstract

BACKGROUND: Evoking spinal release of acetylcholine (ACh) produces antinociception in normal animals and reduces hypersensitivity after nerve injury, and some studies suggest that ACh-mediated analgesia relies on γ-aminobutyric acid (GABA)-ergic signaling in the spinal cord. In this study, the authors tested the spinal mechanisms underlying the antihypersensitivity effects of donepezil, a central nervous system-penetrating cholinesterase inhibitor, in a rat model of neuropathic pain.

METHODS: Male Sprague-Dawley rats were anesthetized, and L5 spinal nerve ligation was performed unilaterally. Withdrawal threshold to a paw pressure test was measured before and after intraperitoneal administration of donepezil, with or without intrathecal antagonists for cholinergic and GABAergic receptors. Microdialysis studies in the ipsilateral dorsal horn of the lumbar spinal cord were also performed to measure extracellular ACh and GABA.

RESULTS: Donepezil increased the withdrawal threshold in spinal nerve ligation rats but not in normal rats. The antihypersensitivity effect of donepezil (1 mg/kg) in spinal nerve ligation rats was reduced by intrathecal pretreatment with atropine (30 μg), a muscarinic receptor antagonist; mecamylamine (100 μg), a nicotinic receptor antagonist; bicuculline (0.03 μg), a γ-aminobutyric acid receptor type A antagonist; and CGP 35348 (30 μg), a γ-aminobutyric acid receptor type B antagonist. ACh and GABA concentrations in the microdialysates from the spinal dorsal horn were increased after intraperitoneal donepezil treatment (1 mg/kg) in both normal and spinal nerve ligation rats.

CONCLUSIONS: Systemic administration of donepezil reduces hypersensitivity after nerve injury by increasing extracellular ACh concentration, which itself induces GABA release in the spinal cord. Activation of this spinal cholinergic-GABAergic interaction represents a promising treatment for neuropathic pain.

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全身应用多奈哌齐通过胆碱能和γ-氨基丁酸机制减轻神经损伤后的高敏反应

【摘要】

背景： 在正常动物中，促进脊髓释放乙酰胆碱可发挥抗伤害作用，减轻脊髓损伤后的高敏反应。一些研究表明乙酰胆碱通过γ-氨基丁酸通路发挥镇痛作用。多奈哌齐是一种可进入中枢神经系统的胆碱酯酶抑制剂，本实验中我们通过大鼠神经病理性疼痛模型，研究多奈哌齐的对抗高敏反应的机制。

方法： 雄性SD大鼠，麻醉后行单侧腰5神经根结扎术。在预先使用或不使用胆碱能和GABA能受体拮抗剂情况下，于腹腔注射多奈哌齐前后，检测大鼠缩足反应的阈值。通过微透析技术检测腰段脊髓同侧脊髓背角细胞外乙酰胆碱和GABA的含量。

结果：多奈哌齐可增加神经根结扎后大鼠的缩足阈值，但对正常大鼠无作用。预先鞘内注射蕈毒碱受体抑制剂阿托品（30 μg)，烟碱受体拮抗剂美卡拉明 (100 μg)，A型γ-氨基丁酸受体拮抗剂荷包牡丹硷(0.03 μg)和B型γ-氨基丁酸受体拮抗剂CGP 35348 (30 μg) 可减轻多奈哌齐（1 mg/kg）在神经根结扎大鼠中的抗高敏反应作用。在正常大鼠和神经根结扎大鼠中，腹腔内注射多奈哌齐后可增加同侧脊髓背角细胞外乙酰胆碱和GABA的含量。

结论： 全身应用多奈哌齐可通过增加细胞外乙酰胆碱含量，进而促进GABA的释放，从而减轻神经损伤后的高敏反应。活化脊髓胆碱能-GABA能受体有希望作为神经病理性疼痛的治疗措施。